Hunter A E, Rogers S Y, Roberts I A, Barrett A J, Russell N
Department of Haematology, City Hospital, Nottingham, UK.
Blood. 1993 Aug 1;82(3):899-903.
We have previously classified the in vitro growth characteristics of clonogenic blasts from patients with acute myeloblastic leukemia (AML) according to their capacity to proliferate autonomously in a blast cell colony assay. Here we have analyzed whether the presence of in vitro autonomous growth characteristics has any clinical relevance in AML. We have studied 50 patients (age 2 to 64 years), all of whom were treated with combination chemotherapy, excluding patients with a history of antecedent myelodysplasia. Leukemic cells from 34 of 50 patients (68%) exhibited either partial or totally autonomous growth in a blast cell colony assay. Cells from the remaining patients exhibited nonautonomous growth and were either totally dependent on exogenous growth factor (n = 8) or failed to proliferate at all in the culture system used (n = 8). All 50 patients were treated by intensive chemotherapy and 69% achieved complete remission (CR). Patients whose blasts exhibited autonomous growth in vitro had a significantly lower CR rate (57%) compared with the 16 patients with nonautonomous growth (94%, P = .02). White blood cell count was the only other significant factor (P = .03), but in multivariate analysis growth characteristics remains the most important predictor of CR. Actuarial relapse risk is 80% and 42% at 5 years for autonomous and nonautonomous groups respectively (P = .1). Overall disease-free survival is 21.8% and is higher in the nonautonomous growth group at 54.2% compared with 11.3% at 5 years (P = .0015) in the autonomous growth characteristics was found to be the single most important indicator of CR and disease-free survival. Our data suggests that the suppression of autocrine growth factor production may be of value in the treatment of AML.
我们之前根据急性髓细胞白血病（AML）患者的克隆性原始细胞在原始细胞集落测定中自主增殖的能力，对其体外生长特征进行了分类。在此，我们分析了体外自主生长特征的存在在AML中是否具有任何临床相关性。我们研究了50例患者（年龄2至64岁），所有患者均接受联合化疗，排除有前期骨髓发育异常病史的患者。50例患者中34例（68%）的白血病细胞在原始细胞集落测定中表现出部分或完全自主生长。其余患者的细胞表现为非自主生长，要么完全依赖外源性生长因子（n = 8），要么在所用培养系统中根本不增殖（n = 8）。所有50例患者均接受强化化疗，69%达到完全缓解（CR）。与16例非自主生长患者（94%，P = .02）相比，其原始细胞在体外表现出自主生长的患者CR率显著较低（57%）。白细胞计数是另一个显著因素（P = .03），但在多变量分析中，生长特征仍然是CR的最重要预测因素。自主生长组和非自主生长组5年时的精算复发风险分别为80%和42%（P = .1）。总体无病生存率为21.8%，非自主生长组较高，5年时为54.2%，而自主生长组为11.3%（P = .0015）。发现自主生长特征是CR和无病生存的单一最重要指标。我们的数据表明，抑制自分泌生长因子的产生可能对AML的治疗有价值。
